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Factors Influencing the Therapeutic Potential of the MSC-derived Secretome

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Abstract

Factors and molecules secreted by mesenchymal stem cells (MSCs) can be termed as “secretome.” The MSC-derived secretome includes growth factors, cytokines, chemokines, immunomodulatory molecules, miRNAs, and extracellular vesicles. The composition of the MSC-derived secretome varies and depends on multiple factors to which the MSCs are exposed to. The manipulation of the content of MSC-derived secretomes can be performed by choosing appropriate donors and applying appropriate preconditioning techniques that are used during cell culturing. Therefore, this review focuses on explaining the effect of donor conditions and certain cell culturing-related manipulations on the MSC-derived secretome content. Aging significantly decreases the quality of the collected MSCs; in fact, it does so in a similar manner to donor collection from a patient. MSC expansion under hypoxic conditions and/or in the presence of inflammatory growth factors releases inflammatory and vasculogenic cytokines, thereby promoting the immunomodulatory properties when applied as a part of a potential MSC-derived secretome therapy. By understanding both the importance of the different donor conditions (such as his/her age and health status) and central role that growth factors play during MSC cell culturing, standardizing MSC-derived secretome production for clinical applications could be better achieved. However, the development and clinical applicability of a large-scale MSC-derived secretome production require further research.

Lay Summary

Donor conditions and the application of certain cell culturing related manipulations during in vitro culturing of mesenchymal stem cells (MSCs) affect the MSC-derived secretome.Preconditioning can alter the MSC extracellular cargo, such as the proteins, growth factors, cytokines, miRNAs, and metabolites. The extracellular cargo is currently used in regenerative medicine for clinical applications. Therefore, it is important to understand the efficacy of preconditioning during the culturing process to standardize MSC-derived secretome production.

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CRS conceived the original idea. AC and GF authored the manuscript. AF and TM reviewed the manuscript.

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Correspondence to Angliana Chouw.

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Chouw, A., Facicilia, G., Sartika, C.R. et al. Factors Influencing the Therapeutic Potential of the MSC-derived Secretome. Regen. Eng. Transl. Med. 8, 384–393 (2022). https://doi.org/10.1007/s40883-021-00242-x

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